Xenoestrogen reduction through diet and supplements

Having suffered from acne and gynecomastia for years I was able to better understand why after getting my 23&Me test results in May this year. After paying a lot of attention to understanding and addressing my methylation shortcomings I've more recently started paying attention to the detox panel results where I have a number of heterozygous and one homozygous mutation on genes that are all responsible for xenobiotic metabolism. Per this table:

I've recently been exploring various articles on xenoestrogens which has led me to looking at DIM and I3C as supplement options but I have a number of remaining queries which I'm sure the more knowledgeable here might have some answers to.

Firstly, I'd rather address the removal of xenoestrogens in a natural and cost effective way through diet. That is, by the incorporation of ample amounts of lightly stir fried cruciferous vegetables (cabbage/brussel sprouts etc.) However the usual question then arises: what quantity do I need to achieve x amount reduction in xenoestrogens. I've not been able to find a clear answer, however this article: http://lpi.oregonstate.edu/infocenter/phytochemicals/i3c/i3crefs.html#ref30 has helped somewhat. It suggests that firstly I3C is a precursor to DIM, and that you need 3 or more times I3C to get the equivalent effect as DIM. It also suggests that glucobrassica is the glucosilonate of interest when looking to obtain DIM or I3C. So it looks like 44gm (half a cup) of brussel sprouts gives 2.4gm/mg of total glucosinolate, of which 10% is likely to be glucobrassica. Therefore 2.4gm x 44gm (105gm of total glucosinolate) will be giving about 10gm of glucobrassica which then goes through processing in the body to yield _some_ amount of DIM.

Indolplex (Md Nutritionals) gives 20gm of 'bioavailable' DIM per capsule. So the one query left here is how much DIM is my body likely to yield from that 10gm dose of glucobrassica, and in broader terms is it likely to be hopeless in terms of getting a therapeutic dose (dose that actually changes hormones) If this is the case then how does that reconcile with the seemingly common knowledge that populations eating these vegetables have significantly better xenoestrogen profiles (or am I mistaking that for cancer risk which could be due to all the other phytonutrients in these vegetables..)

So the next question is what kind of estrogen reduction is likely for a given dosage of DIM. Naturally if we're all going to start playing with our hormones it might be helpful to know what kind of dosage is needed to achieve a certain result.... This is one article I found http://www.ncbi.nlm.nih.gov/pubmed/15623462?dopt=Abstract
however I can't find the actual results. It seems that anywhere from 100-400gm of DIM is recommended by way of a therapeutic dosage for men, but wheres the data to show what kind of estrogen reduction correlates with dosage level... If anyone can shed light on this I'm sure many forum users would be grateful - I know I will .-)

I know practically nothing about genes, but since I see some of your mutations are on CYP1A1 and CYP1A2, I thought you might be interested in this book about porphyria.http://books.google.com/books?id=4A...wQ6AEwAA#v=onepage&q=cyp1A1 porphyria&f=false
Porphyria brings with it many similarities to methylation problems, and can be brought on by mostly the same triggers. I see that there are different variations to each gene, and I don't know how to figure out if the ones in your panel are the ones in an Acute Intermittent Porphyria panel.

The main reason I took the time to try to find this information for you,(and it always turns out that when I find something like this it helps me, too) is because of your desire to try to lower estrogens using the brassica family of vegetables. Although they are definitely a politically correct way to get healthy, they can have a negative side effect on the liver and conversion of T4 to T3 in the liver. That happens almost universally in people with porphyria, but also in people who do not have porphyria. The reason is related to a chemical that brassica vegetables (and some fruit and legumes...peanuts, soy) contain that induce Phase I liver detoxification, which induces CYP 450 enzyme production. CYP 450 enzymes need heme, so inducing production induces heme production. When that occurs, and you have a genetic defect that affects one of the enzymes used along the way, heme production is never brought to completion, so heme production is over induced. That causes porphyrin build up, which causes a lot of pain and suffering. (porphyria)

This is just a heads up; if the brassica vegetables bother you, you will probably be able to tell fairly quickly. For me, the first thing I notice is a hoarse or froggy voice. If I ignore that, I usually get abdominal pain accompanied by a headache and anxiety.

The main reason I took the time to try to find this information for you,(and it always turns out that when I find something like this it helps me, too) is because of your desire to try to lower estrogens using the brassica family of vegetables. Although they are definitely a politically correct way to get healthy, they can have a negative side effect on the liver and conversion of T4 to T3 in the liver. That happens almost universally in people with porphyria, but also in people who do not have porphyria. The reason is related to a chemical that brassica vegetables (and some fruit and legumes...peanuts, soy) contain that induce Phase I liver detoxification, which induces CYP 450 enzyme production. CYP 450 enzymes need heme, so inducing production induces heme production. When that occurs, and you have a genetic defect that affects one of the enzymes used along the way, heme production is never brought to completion, so heme production is over induced. That causes porphyrin build up, which causes a lot of pain and suffering. (porphyria)

This is just a heads up; if the brassica vegetables bother you, you will probably be able to tell fairly quickly. For me, the first thing I notice is a hoarse or froggy voice. If I ignore that, I usually get abdominal pain accompanied by a headache and anxiety.

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I'd never heard of this condition till reading this post but now I have read it here: http://en.wikipedia.org/wiki/Porphyria I'm fairly sure I don't have it thank God. I've been eating fairly large amounts of cabbage and brussel sprouts for almost 1.5 years now and I don't get any severe abdominal symptoms, blistering from sun exposure etc. Besides - surely theres a gene that the 23&Me panel already covers which would have been noted in my results if I had this condition... no?

Tell you what though - I've just had generic blood tests a week ago which includes RBC and haemoglobin so those would be distorted if porphyria were my issue I'm guessing (depressed hemaglobin / RBC's) ?

Useful knowledge in any event.. perhaps I can increase my capacity for aerobic exercise with cruciferous veges through the upregulated heme production?

I can't describe what a eureka moment this is Gestalt - thanks for having the wit to quickly see my profile/queries and identify a likely solution: As I look over the first link describing the girl with almost identical detox SNP's as myself and psoriasis I realise this is going somewhere. I have very dry skin and chronic itchiness - particularly following fatty meals such as the one I've just eaten! In fact I've just come to read this post after applying cortisone cream to the psoriasis outbreak in the middle of my chest and having smeared myself in shea butter in attempts to keep my skin from drying out!

Then I look over that handwritten diagram showing the relevance of CYP1B1 and CYP1A2 in estrogen excretion and realise my body must have one of the worst gene combinations for estrogen processing! Which in turn explains the gynecomastia issues I've been enduring for so long now (and in spite of doing everything 'right')

Furthermore: the link re: Cholecystitis: BAM another eureka moment. My mother and her mother had serious gall bladder issues (stones) which in fact led to her having it removed 10 years ago now. Moreover, I have the most insatiable itching problems which I notice have become worse more recently as I've introduced substantial quantities of black pepper into my diet as a means to minimise iron uptake (I tend towards high levels) I also notice this itchiness is far worse after a specific meal I eat which is far higher in fat than my usual dinner fare..

Its such a shame the 23&Me detox panel doesn't come with an interpretation that could have helped me learn of this issue earlier: Someone from these very forums was helpful enough to give me an interpretation but I was misunderstood re: the CYP1B1 mutation which I understood to mean I produced a deficiency of this enzyme rather than the excess that it must be?!

I was about to embark on a few dietary changes such as cutting out or minimising black pepper and substituting it for green tea which will keep my iron uptake to a minimum, but I seem to recall something about quinone excess and that my gene combo (which you can liken almost identically to the girl in your links) leads to an excess of these already?!

PS - I just saw a Dr to receive basic blood test results and there was elevation of the AST enzyme beyond the normal range. Any theories as to the potential relevance?

Have just read the 'fake estrogens' article - am liking your holistic approach to this whole area where many are simply fixated purely on the epigenetics and ignore the relevance of orthomolecular medicine and other niche areas which all have small but useful contributions to make imho...

You might want to go with cutting out black pepper completely, which I will try to find a link to explain as my brain is going through gluten/grain withdrawal. Also, with the CYP1A2, you might experience some relief with cutting out the brassica vegetables. As you can see they haven't helped the gynecomastia anyway. The brassicas put too much stress on the Phase I detoxification system, which in your case (and mine, too) needs relief.

Exellent work, Gestalt, although I am having a hard time understanding it all. I won't give up on trying to understand it, though.

You might want to go with cutting out black pepper completely, which I will try to find a link to explain as my brain is going through gluten/grain withdrawal. Also, with the CYP1A2, you might experience some relief with cutting out the brassica vegetables. As you can see they haven't helped the gynecomastia anyway. The brassicas put too much stress on the Phase I detoxification system, which in your case (and mine, too) needs relief.

Exellent work, Journeyman, although I am having a hard time understanding it all. I won't give up on trying to understand it, though.

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Thanks for reminding me of that CYP1A2 consideration Violeta.... hmm this creates quite a dilemma where cruciferous vegetables and DIM supplementation appear to be my main plan of attack in helping offset my genetic tendency to accumulate xenoestrogens..... More grapefruit and reservatrol and perhaps just eat the cruciferous veges rather than buying the DIM?

Errrr I just did a search for the CYP1A2 and it seems it might be a bumsteer in the genetic genie translation of the 23&me results and should read CYP1A1 ? At least this is what Caledonia's post suggests and she seems quite well clued up on these matters.... I think we need to clarify this - especially where our treatments could go down very different routes depending on whether this is the case.

Thanks for reminding me of that CYP1A2 consideration Violeta.... hmm this creates quite a dilemma where cruciferous vegetables and DIM supplementation appear to be my main plan of attack in helping offset my genetic tendency to accumulate xenoestrogens..... More grapefruit and reservatrol and perhaps just eat the cruciferous veges rather than buying the DIM?

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Actually, the brassicas contain sulforaphane which is the problem, and DIM doesn't. Well, check this article and see what you think. As I said before, my brain is fuzzy and I can make errors.

Am I missing something re: the CYP1A2 issue. From what I can tell my gene defect means reduced activity of this enzyme which is responsible for xenobiotic metabolism. Therefore I see little reason to be concerned about its induction by cruciferous veges. Indeed that is what I'm trying to achieve...

After those breasts have been enlarged for a few years, assuming it includes glandular growth, changing estrogens content won't decrease established tissue. Fat can be lost. Fat transforms testosterone to estrogen. Estrogen however is meant to be in balance and affects health and weight. Be careful and research more carefully. Also the deadlock quartet affects hormones. I have been on testosterone injections for 13 years as mine went through the floor with b12 deficiency and never came back.

After those breasts have been enlarged for a few years, assuming it includes glandular growth, changing estrogens content won't decrease established tissue. Fat can be lost. Fat transforms testosterone to estrogen. Estrogen however is meant to be in balance and affects health and weight. Be careful and research more carefully. Also the deadlock quartet affects hormones. I have been on testosterone injections for 13 years as mine went through the floor with b12 deficiency and never came back.

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Quite right Fredd - I understand that once the tissues are formed the level of hormone variation will do little. What I should be referring to (and the intention) was the excess estrogen symptoms in general. As to your point about research I feel confident now that my CYP1A2 polymorphism advocates the intake of I3C and DIM promoting foods such as brussel sprouts / brocolli etc. This seems to clarify the issue quite clearly: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784188/

Hey journeyman, I also have similar polymorphisms as you.
CYP1A2 and CYP1B1. I don't know my estrogen levels, but I also have had a history of moderate acne but no gynecomastica. My liver enzymes are always in the normal ranges, but my bilirubin is always elevated due to what my doctor tells me is from Gilbert's Syndrome. People with gilberts gave trouble with phase II metabolism and Glucuronidation, which is involved in the metabolism of substances such as drugs, pollutants, bilirubin, androgens, estrogens, mineralocorticoids, glucocorticoids, fatty acid derivatives, retinoids, and bile acids(wiki).

See what you think about what this might mean with respect to estrogens.
BTW, have you had your thyroid checked?

I don't know that it corrects the morphism of the cyp1a1 or cyp1a2, and if it doesn't, what happens?

The Chinese lady that taught me about liver and estrogen told me it's important to clean the liver. That might make it more effective at removing estrogens. That might get your AST down, too.

Also, maybe if one doesn't have adequate methylation to ensure removal of the breakdown products.....? And do you know why you are overproducing estrogen?

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Now I think I understand your concerns re: cruciferous vege intake and the CYP1A2 impact. However I think I have an understanding having read another article which explained that there are a number of different glucosinolates within cruciferous veges and that whilst some actually inhibit the Cyp1A2 the overall effect (due to the many other types of glucosinolates) is very much an upregulation of this enzyme and therefore better estrogen metabolism..

With regard to the notion of any of these veges 'correcting' the relevant polymorphism's they don't. Its all about increasing the output of these enzymes which don't work efficiently (or work too efficiently) due to the polymorphisms.

Ps - chinese medicine has a lot to offer in combination with nutritional genomics... am now considering a liver/gall bladder flush in addition to the coffee enema's I'm currently doing to increase my GST activity...

Hey journeyman, I also have similar polymorphisms as you.
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CYP1A2 and CYP1B1. I don't know my estrogen levels, but I also have had a history of moderate acne but no gynecomastica. My liver enzymes are always in the normal ranges, but my bilirubin is always elevated due to what my doctor tells me is from Gilbert's Syndrome. People with gilberts gave trouble with phase II metabolism and Glucuronidation, which is involved in the metabolism of substances such as drugs, pollutants, bilirubin, androgens, estrogens, mineralocorticoids, glucocorticoids, fatty acid derivatives, retinoids, and bile acids(wiki).

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Well you don't do things by halves BFG. You're either homozygous or completely unaffected in terms of your polymorphism's! Out of interest: have you got the GSTT1 gene? Further: have you ever done the genotype tests per Peter D'Adamo's theory. I'd be interested to see if theres any trend re: the genetic types identified by D'Adamo and gene results. Imagine being able to look at someone and be able to tell by their relative limb proportions their likely genetic makeup....

I'm now coming to the end of day two on my new diet which coincides with day 4 of my substantially increased methylation protocol. This diet precludes black pepper and cumin in the interests of minimising beta glucoronidase activity. It includes significant quantities of steamed cruciferous vegetables: namely brussel sprouts and brocolli which have the highest relative concentrates of the precursors to DIM.

I did my second coffee enema in two days (more than my usual once a week routine) and noticed an unusual wave of nausea some 3 hours after the enema which caused me to defecate again giving some relief. I also noticed my sleep being interrupted with unusually improved circulation to my *ahem* and 'urge' so: as uncomfortable as the wave of nausea was today I think it might be indicative of some substantial improvement in what must be metabolic cholestatic pruritis.. Interestingly that severe and incurable itchiness I was speaking of just 2 days ago is all but gone now which I suspect confirms that the bile salts were leaking into my bodily fluids and causing the itching referred to in this brilliant article that Gestalt was kind enough to bring to my attention earlier in this thread: http://www.gestaltreality.com/2013/09/21/metabolic-cholestatic-pruritus/

I'm now keen to know whether these symptoms are indicative of the estrogen excretion and clearing of of my biliary problems in the way I currently suspect. Additionally, would a liver/gall bladder flush per http://www.liverdoctor.com/liver-problems/gallbladder/ (scroll most of the way down the page) be a good idea to help clear up my liver. I think the last time I did this flush was 2007 where I had hundreds of the small green stones (which I understand are not stones but in fact facalithes? ) and which nonetheless clear out the liver....